Image-guided percutaneous bone biopsy for pediatric osteomyelitis: correlating MRI findings, tissue pathology and culture, and effect on clinical management.

Bone biopsy remains the gold standard for diagnosis of osteomyelitis while MRI results in a radiologic diagnosis that generally precedes biopsy. This study's purpose is to examine the diagnostic yield and effect of biopsy results on clinical management in children with suspected osteomyelitis and positive MRI findings. A retrospective review was performed at a tertiary care children's hospital. Search of the EMR and radiology PACS identified patients below 18 years who underwent bone biopsy with interventional radiology for osteomyelitis and had positive MRI findings for osteomyelitis prior to biopsy. Data was collected on patient demographics, MRI findings, biopsy procedural details, tissue culture, histopathology results, and clinical management before and after biopsy. Changes in management were categorized as antibiotic type/quantity, duration, or diagnosis. A total of 82 biopsies in 79 patients with suspicion for osteomyelitis and positive MRIs prior to biopsy were performed over 5 years from 2014 to 2019. All biopsies were successful and sent for tissue culture. 22/82 biopsies (27%) yielded positive cultures. Of those with tissue cultures, 16/22 (72%) resulted in change in clinical management. Of all biopsies, 18/82 (22%) resulted in a change in management (15 antibiotic, 1 duration, 2 diagnosis). The 2 changes in diagnosis included one biopsy done which was positive for cancer and a second which was found to not demonstrate osteomyelitis on histology. In the pediatric population, bone biopsy is a reasonably low morbidity procedure. However, there is a relatively low rate of positive tissue cultures even with MRI findings suspicious for osteomyelitis. Approximately 1 in 5 biopsies resulted in a change in clinical management, mostly in antibiotic selection. Bone biopsy may have a higher clinical impact in pre-specified circumstances.

Nutrient Sensing via Gut in Drosophila melanogaster.

Nutrient-sensing mechanisms in animals' sense available nutrients to generate a physiological regulatory response involving absorption, digestion, and regulation of food intake and to maintain glucose and energy homeostasis. During nutrient sensing via the gastrointestinal tract, nutrients interact with receptors on the enteroendocrine cells in the gut, which in return respond by secreting various hormones. Sensing of nutrients by the gut plays a critical role in transmitting food-related signals to the brain and other tissues informing the composition of ingested food to digestive processes. These signals modulate feeding behaviors, food intake, metabolism, insulin secretion, and energy balance. The increasing significance of fly genetics with the availability of a vast toolbox for studying physiological function, expression of chemosensory receptors, and monitoring the gene expression in specific cells of the intestine makes the fly gut the most useful tissue for studying the nutrient-sensing mechanisms. In this review, we emphasize on the role of Drosophila gut in nutrient-sensing to maintain metabolic homeostasis and gut-brain cross talk using endocrine and neuronal signaling pathways stimulated by internal state or the consumption of various dietary nutrients. Overall, this review will be useful in understanding the post-ingestive nutrient-sensing mechanisms having a physiological and pathological impact on health and diseases.

Water Oxidation by the [Co4O4(OAc)4(py)4](+) Cubium is Initiated by OH(-) Addition.

The cobalt cubium Co4O4(OAc)4(py)4(ClO4) (1A(+)) containing the mixed valence [Co4O4](5+) core is shown by multiple spectroscopic methods to react with hydroxide (OH(-)) but not with water molecules to produce O2. The yield of reaction products is stoichiometric (>99.5%): 41A(+) + 4OH(-) → O2 + 2H2O + 41A. By contrast, the structurally homologous cubium Co4O4(trans-OAc)2(bpy)4(ClO4)3, 1B(ClO4)3, produces no O2. EPR/NMR spectroscopies show clean conversion to cubane 1A during O2 evolution with no Co(2+) or Co3O4 side products. Mass spectrometry of the reaction between isotopically labeled µ-(16)O(bridging-oxo) 1A(+) and (18)O-bicarbonate/water shows (1) no exchange of (18)O into the bridging oxos of 1A(+), and (2) (36)O2 is the major product, thus requiring two OH(-) in the reactive intermediate. DFT calculations of solvated intermediates suggest that addition of two OH(-) to 1A(+) via OH(-) insertion into Co-OAc bonds is energetically favored, followed by outer-sphere oxidation to intermediate [1A(OH)2](0). The absence of O2 production by cubium 1B(3+) indicates the reactive intermediate derived from 1A(+) requires gem-1,1-dihydoxo stereochemistry to perform O-O bond formation. Outer-sphere oxidation of this intermediate by 2 equiv of 1A(+) accounts for the final stoichiometry. Collectively, these results and recent literature (Faraday Discuss., doi:10.1039/C5FD00076A and J. Am. Chem. Soc. 2015, 137, 12865-12872) validate the [Co4O4](4+/5+) cubane core as an intrinsic catalyst for oxidation of hydroxide by an inner-sphere mechanism.

Dopamine-Dependent Plasticity Is Heterogeneously Expressed by Presynaptic Calcium Activity across Individual Boutons of the Drosophila Mushroom Body.

The Drosophila mushroom body (MB) is an important model system for studying the synaptic mechanisms of associative learning. In this system, coincidence of odor-evoked calcium influx and dopaminergic input in the presynaptic terminals of Kenyon cells (KCs), the principal neurons of the MB, triggers long-term depression (LTD), which plays a critical role in olfactory learning. However, it is controversial whether such synaptic plasticity is accompanied by a corresponding decrease in odor-evoked calcium activity in the KC presynaptic terminals. Here, we address this question by inducing LTD by pairing odor presentation with optogenetic activation of dopaminergic neurons (DANs). This allows us to rigorously compare the changes at the presynaptic and postsynaptic sites in the same conditions. By imaging presynaptic acetylcholine release in the condition where LTD is reliably observed in the postsynaptic calcium signals, we show that neurotransmitter release from KCs is depressed selectively in the MB compartments innervated by activated DANs, demonstrating the presynaptic nature of LTD. However, total odor-evoked calcium activity of the KC axon bundles does not show concurrent depression. We further conduct calcium imaging in individual presynaptic boutons and uncover the highly heterogeneous nature of calcium plasticity. Namely, only a subset of boutons, which are strongly activated by associated odors, undergo calcium activity depression, while weakly responding boutons show potentiation. Thus, our results suggest an unexpected nonlinear relationship between presynaptic calcium influx and the results of plasticity, challenging the simple view of cooperative actions of presynaptic calcium and dopaminergic input.

Tracking Sugar-Elicited Local Searching Behavior in Drosophila.

Foraging behavior is essential for the survival of organisms as it enables them to locate and acquire essential food resources. In Drosophila, hunger triggers a distinct search behavior following the consumption of small quantities of a sugar solution. This report presents a simple experimental setup to study sugar-elicited search behavior with the aim of uncovering the underlying mechanisms. Minute quantities of concentrated sugar solution elicit sustained searching behavior in flies. The involvement of path integration in this behavior has been established, as flies utilize their trajectory to return to the sugar location. The most recent findings provide evidence of temporal modulation in the initiation and intensity of the search behavior after sugar intake. We have also used this setup for artificial activation of specific taste-receptor neurons in the pharynx, which elicits the search behavior. The Drosophila neurogenetic toolkit offers a diverse array of tools and techniques that can be combined with the sugar-elicited search behavior paradigm to study the neural and genetic mechanisms underlying foraging. Understanding the neural basis of hunger-driven searching behavior in flies contributes to the field of neurobiology as a whole, offering insights into the regulatory mechanisms that govern feeding behaviors not only in other organisms but also in humans.

Whole Scalp Radiation Therapy for Recurrent Benign Cylindromas.

Cylindromas are a rare benign pathology that can manifest as multiple lesions on a patient's scalp. Standard of care is resection of lesions. We report a case of a 74-year-old man with a known diagnosis of Brooke-Spiegler syndrome which is a genetic syndrome that results in multiple recurrent cylindromas. He had approximately 70 prior resections to remove recurrent lesions with multiple grafts. After a large scalp recurrence, with multiple satellite areas, he preferred radiation to the largest site for no-surgical management. After an excellent clinical response, this led to him electing for total scalp irradiation to the remaining sites. He now has a complete response to all remaining sites.

Modulation of sugar feeding behavior by Gymnema sylvestre in Drosophila melanogaster.

INTRODUCTION: Sugar is the main source of energy for nearly all animals. However, consumption of a high amount of sugars can lead to many metabolic disorders hence, balancing calorie intake in the form of sugar is required. Various herbs are in use to control body weight, cure diabetes and control elevated blood sugar levels. One such herb is Gymnema sylvestre commonly called Gurmar (destroyer of sugar). Gurmar selectively inhibits sugar sensation by mechanisms that are still elusive. OBJECTIVES: The primary objective of this study is to understand the effect of gurmar on sweet taste feeding behaviour in insects using the invertebrate model system Drosophila melanogaster. METHODS: For this study, we used feeding assays, spectrophotometry and Proboscis Extension Reflex (PER) assay to determine how flies detect gurmar. Additionally, life span analysis, egg-laying behaviour and developmental profiles were used to probe the role of gurmar on the overall health of the flies. During the whole study, we used only the raw powdered form of gurmar (dried leaves) to examine its effect on sweet taste feeding behaviour. RESULTS: Our data demonstrate that whole gurmar in a raw powdered form is aversive to flies and inhibits sugar evoked PER and feeding responses. Also, we observed it takes at least 24 h of starvation time to reduce the consumption of sugar in flies pre-fed on gurmar. Flies lay a fewer number of eggs on gurmar media and show developmental defects. Our data suggest that flies detect gurmar using both taste and olfactory cues. CONCLUSION: Understanding how gurmar reshapes taste curves to promote reduced consumption of sugars in flies will open up avenues to help people with health issues related to high sugar consumption, but our data also highlights that its consumption should be carefully considered since gurmar is aversive to flies and has detrimental effects on development.

Aortoesophageal fistula treated with emergent thoracic stent grafting.

Aortoesophageal fistula (AEF) is a rare pathology with a poor prognosis. Historically, open repair approaches were undertaken. With the advent of endovascular techniques, alternative methods such as thoracic endovascular aortic repair (TEVAR) have emerged. This case describes a patient who presented with severe hematemesis and, upon imaging, an AEF was discovered. Urgent TEVAR was indicated with a graft oversized to the native aorta by 10% to 15%, along with coil embolization of the intercostal artery. We report here on the successful management of AEF via TEVAR.

Endovascular treatment of traumatic azygous vein injuries: a case report.

BACKGROUND: Management of thoracic vascular injury predominantly focuses on the aorta and its tributaries while reports of venous injury are less frequent. Although rare, traumatic azygous vein injuries are associated with high mortality. Prompt treatment is required and has traditionally been open surgery. We present a case of an endovascular repair of an azygous vein injury. CASE PRESENTATION: A female patient presented to our trauma center following ejection after a motor vehicle collision (MVC). CT imaging workup revealed mediastinal and periaortic hematoma with active contrast extravasation adjacent to the azygos vein. She was referred to interventional radiology for vascular evaluation and potential endovascular intervention. The patient met criteria for class III hypovolemic shock upon arrival in the endovascular suite. Aortography demonstrated no arterial injury. Venography revealed a pseudoaneurysm on the superior aspect of the azygos arch and contrast extravasation from the inferior margin of the azygous arch. A stent-graft was deployed and post-deployment venogram showed no extravasation and successful exclusion of the injuries. The patient did not have further signs of bleeding. She left the interventional suite with improved vital signs, yet her condition remained guarded. Follow-up CT chest confirmed continued patency of the stent-graft at 8 days and 2 years post-procedure. CONCLUSION: Historically, azygos vein injuries are a rare occurrence and managed with open surgery. Swift management is necessary to prevent the increased morbidity and mortality associated with azygous vein injury, particularly in polytrauma patients such as the one presented here. We believe endovascular stent-graft treatment offers an innovative alternative to the current standard of operative management of azygos vein injury.

Starvation and activity dependent modulation of salt taste behavior in Drosophila.

Background: Sodium present in NaCl is a fundamental nutrient required for many physiological processes but high salt consumption in western world is contributing health risk to all age individuals. Although high salt detection pathways have been studied in great detail, the mechanisms that regulate high salt consumption in animals are largely unknown. To understand how pre-exposure to high NaCl diet modulates subsequent feeding behavior, we looked into the neural mechanisms of high NaCl consumption in adult Drosophila. Method: We used Neuro-Genetics, imaging and behavioral assays to determine how flies respond to high NaCl exposure. Result: We studied the neural mechanism by which flies modify their acceptance of high salt as a function of diet, where a long-term high-salt exposure increases taste sensitivities of pharyngeal LSO (Labral sense organ) neurons and enhances high salt intake. We discovered that exposing flies to high NaCl diet(200mM NaCl in fly food) for three days modify their feeding responses to high levels of salt. High NaCl fed flies show decline in high salt aversion under starvation. Genetic suppression of LSO pharyngeal neurons in high NaCl fed flies inhibits excessive salt intake. We found that this modulation requires functional LSO neurons and starvation state, and that multiple independent taste receptor neurons and pathways are involved in this process. Silencing any one of multiple LSO neuronal types inhibits excessive salt intake. Conclusion: Our data support the idea that high dietary salt modulates and reshapes salt and other taste curves to promote over consumption of food in flies. Our study suggest flies can adapt to the amount of salt ingested over several days, indicating the presence of a critical mechanism to reset the salt appetite and related neural circuits. Identification of new molecular sensors for salt and related neural controls such as hormones, neuropeptides, and neurotransmitters may yield insights into the coordination of processes in the nervous system.

Fluoresceinated Aminohexanol Tethered Inositol Hexakisphosphate: Studies on Arabidopsis thaliana and Drosophila melanogaster and Docking with 2P1M Receptor.

Inositol hexakisphosphate (InsP6; phytic acid) is considered as the second messenger and plays a very important role in plants, animals, and human beings. It is the principal storage form of phosphorus in many plant tissues, especially in dry fruits, bran, and seeds. The resulting anion is a colorless species that plays a critical role in nutrition and is believed to cure many diseases. A fluoresceinated aminohexanol tethered inositol hexakisphosphate (III) had been synthesized earlier involving many complicated steps. We describe here a simple two-step synthesis of (III) and its characterization using different techniques such as matrix-assisted laser desorption ionization mass spectrometry, tandem mass spectrometry, and Fourier transform infrared, ultraviolet-visible, ultraviolet-fluorescence, 1H nuclear magnetic resonance (NMR), and two-dimensional NMR spectroscopies. The effect of (III) has been investigated in the model systems, Arabidopsis thaliana and Drosophila melanogaster. Using Schrodinger software, computational studies on the binding of (III) with the protein 2P1M (Auxin-receptor TIR1-adaptor ASK1 complex) has revealed strong binding propensity with this compound. These studies on the fluoresceinated tethered phytic acid could have far reaching implications on its efficacy for human health and treatment of diseases (cancer/tumor and glioblastoma) and for understanding phosphorous recycling in the environment, especially for plant systems.

Salt an Essential Nutrient: Advances in Understanding Salt Taste Detection Using Drosophila as a Model System.

Taste modalities are conserved in insects and mammals. Sweet gustatory signals evoke attractive behaviors while bitter gustatory information drive aversive behaviors. Salt (NaCl) is an essential nutrient required for various physiological processes, including electrolyte homeostasis, neuronal activity, nutrient absorption, and muscle contraction. Not only mammals, even in Drosophila melanogaster, the detection of NaCl induces two different behaviors: Low concentrations of NaCl act as an attractant, whereas high concentrations act as repellant. The fruit fly is an excellent model system for studying the underlying mechanisms of salt taste due to its relatively simple neuroanatomical organization of the brain and peripheral taste system, the availability of powerful genetic tools and transgenic strains. In this review, we have revisited the literature and the information provided by various laboratories using invertebrate model system Drosophila that has helped us to understand NaCl salt taste so far. We hope that this compiled information from Drosophila will be of general significance and interest for forthcoming studies of the structure, function, and behavioral role of NaCl-sensitive (low and high concentrations) gustatory circuitry for understanding NaCl salt taste in all animals.